CN101402650B - Organotin coordination compound, preparation and uses thereof - Google Patents
Organotin coordination compound, preparation and uses thereof Download PDFInfo
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- CN101402650B CN101402650B CN2008101403911A CN200810140391A CN101402650B CN 101402650 B CN101402650 B CN 101402650B CN 2008101403911 A CN2008101403911 A CN 2008101403911A CN 200810140391 A CN200810140391 A CN 200810140391A CN 101402650 B CN101402650 B CN 101402650B
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 208000005718 Stomach Neoplasms Diseases 0.000 claims abstract description 7
- 206010017758 gastric cancer Diseases 0.000 claims abstract description 7
- 201000011549 stomach cancer Diseases 0.000 claims abstract description 7
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims abstract description 6
- 208000032839 leukemia Diseases 0.000 claims abstract description 6
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 5
- 201000011216 nasopharynx carcinoma Diseases 0.000 claims abstract description 5
- 201000007270 liver cancer Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 41
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 18
- 239000003208 petroleum Substances 0.000 abstract description 12
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 abstract description 11
- 230000001093 anti-cancer Effects 0.000 abstract description 6
- 239000013078 crystal Substances 0.000 abstract description 6
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 abstract description 6
- 239000007787 solid Substances 0.000 abstract description 6
- 201000009030 Carcinoma Diseases 0.000 abstract 1
- 230000002440 hepatic effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 9
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 229940041181 antineoplastic drug Drugs 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000002390 rotary evaporation Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910020813 Sn-C Inorganic materials 0.000 description 2
- 229910018732 Sn—C Inorganic materials 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- XJLXINKUBYWONI-NNYOXOHSSA-O NADP(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-O 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 229910020923 Sn-O Inorganic materials 0.000 description 1
- 229910009053 Sn—O—Sn Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000012844 infrared spectroscopy analysis Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 231100000338 sulforhodamine B assay Toxicity 0.000 description 1
- 238000003210 sulforhodamine B staining Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an organic tin coordination compound with the constitutional formula as shown. The preparation method of the compound comprises the steps: 1mmol of dibutyltin oxide, 1mmol to 1.5mmol of 2-cinchoninic acid and 30ml to 50ml of benzene are added into a flask, stirred and refluxed for 5h to 7h at the temperature of 45 DEG C to 50 DEG C, cooled to the normal temperature, then rotated and evaporated to obtain white solids which are then recrystallized with ether-petroleum ether to obtain colorless transparent crystals, namely, the organic tin coordination compound, wherein, the volume ratio of the ether and the petroleum ether is 1: 1 to 2: 1. The organic tin coordination compound can be used for preparing medicaments which cure stomach cancer, nasopharyngeal carcinoma, human hepatic carcinoma or leukaemia, and is characterized by higher anti-cancer activity, good fat solubility, low cost, simple preparation method, etc.
Description
Technical Field
The invention relates to an organic tin coordination compound, a preparation method thereof and application of the compound in preparing anti-cancer drugs.
Background
The research on organotin compounds dates back to the fortieth of the nineteenth century, but the actual prosperity of organotin chemistry began in the 80 th of the 20 th century, when some dialkyltin compounds were found to have higher antitumor activity than cisplatin during the research and screening of metal anticancer drugs (crown, a.j.; Smith, p.j.; atasi.g., chem.biol.interact., 1980, 32, 171). Since then, as the research on organotin compounds is being carried out, the research field and application range of organotin chemistry are expanding.
Disclosure of Invention
In view of the above prior art, the present invention provides a novel organotin complex, a method for preparing the same, and applications thereof.
An organotin complex having the formula:
wherein,nbu represents n-butyl.
A method for preparing an organotin complex: adding 1mmol of dibutyltin oxide, 1-1.5 mmol of 2-quinolinecarboxylic acid and 30-50 ml of benzene into a flask, stirring and refluxing for 5-7 hours at the temperature of 45-50 ℃, cooling to room temperature, and performing rotary evaporation to obtain a white solid; recrystallizing with diethyl ether-petroleum ether to obtain colorless transparent crystal, i.e. organic tin coordination compound; wherein the volume ratio of the diethyl ether to the petroleum ether is 1: 1-2: 1.
the reaction formula is as follows:
the organotin coordination compound is applied to the preparation of medicines for treating gastric cancer, nasopharyngeal carcinoma, human liver cancer or leukemia.
The molecular formula of the organotin coordination compound of the invention is C72H96N4O10Sn4(ii) a Has molecular weight of 1652.29, has high anticancer activity, and can be used as raw material for preparing medicine for treating gastric cancer, nasopharyngeal carcinoma, hepatocarcinoma or leukemia. Compared with the platinum anticancer compounds commonly used at present, the organic tin coordination compound has the characteristics of higher anticancer activity, good lipid solubility, low cost, simple preparation method and the like, and provides a new way for developing anticancer drugs.
Detailed Description
The invention is further illustrated by the following examples:
example 1: preparing an organotin complex: adding 1.0mmol of dibutyltin oxide, 1.0mmol of 2-quinolinecarboxylic acid and 30ml of benzene into a flask, stirring and refluxing for 6 hours at the temperature of 45 ℃, cooling to room temperature, and performing rotary evaporation to obtain a white solid; recrystallizing with diethyl ether-petroleum ether to obtain colorless transparent crystal, i.e. organic tin coordination compound; wherein the volume ratio of the diethyl ether to the petroleum ether is 1: 1. the yield is 85%, and the melting point is 192-194 ℃.
The results of infrared spectroscopic analysis and nuclear magnetic resonance analysis are as follows:
infrared Spectrum (KBr, cm)-1)：vas(C＝O)1589，vs(C-O)1381，vas(Sn-C)588，vs(Sn-C)533，v(Sn-O)460，v(Sn-N)451，v(Sn-Cl)263，v(Sn-O-Sn)621。
1H nuclear magnetism (CDCl)3，ppm)：1H nuclear magnetism (CDCl)3，ppm)：δ8.85(d，1H，H-3)，8.32(d，1H，H-4)，8.26(d，1H，H-9)，8.11(d，1H，H-6)，7.80(dd，1H，H-8)，7.74(dd，1H，H-7)，0.88-1.81(m，12H，Sn-C4H9)。13Nuclear magnetic resonance (CDCl)3，ppm)：δ172.3，156.9，145.5，133.7，139.1，132.4，129.6，127.6，126.1，(C9H6NO2)；22.8，31.7，45.3(-CH2-)，14.3(-CH3)；δ168.1(COO)。
Elemental analysis: calculated value C72H96N4O10Sn4: c, 52.33; h, 5.86; n, 3.39; measured value: c, 52.27; h, 5.95; and N, 3.47%.
Example 2: preparing an organotin complex: adding 1.0mmol of dibutyltin oxide, 1.5mmol of 2-quinolinecarboxylic acid and 50ml of benzene into a flask, stirring and refluxing at 45 ℃ for 7 hours, cooling to room temperature, and performing rotary evaporation to obtain a white solid; recrystallizing with diethyl ether-petroleum ether to obtain colorless transparent crystal, i.e. organic tin coordination compound; wherein the volume ratio of the diethyl ether to the petroleum ether is 1: 1. the yield is 80%, and the melting point is 192-194 ℃.
Example 3: preparing an organotin complex: adding 1.0mmol of dibutyltin oxide, 1.0mmol of 2-quinolinecarboxylic acid and 50ml of benzene into a flask, stirring and refluxing for 6 hours at the temperature of 50 ℃, cooling to room temperature, and performing rotary evaporation to obtain a white solid; recrystallizing with diethyl ether-petroleum ether to obtain colorless transparent crystal, i.e. organic tin coordination compound; wherein the volume ratio of the diethyl ether to the petroleum ether is 2: 1. The yield is 82%, and the melting point is 192-194 ℃.
Example 4: preparing an organotin complex: adding 1.0mmol of dibutyltin oxide, 1.3mmol of 2-quinolinecarboxylic acid and 40ml of benzene into a flask, stirring and refluxing for 5 hours at the temperature of 48 ℃, cooling to room temperature, and performing rotary evaporation to obtain a white solid; recrystallizing with diethyl ether-petroleum ether to obtain colorless transparent crystal, i.e. organic tin coordination compound; wherein the volume ratio of the diethyl ether to the petroleum ether is 2: 1. The yield is 82%, and the melting point is 192-194 ℃.
Test example: the determination of the in vitro anticancer activity of the organotin coordination compound is realized by two experimental methods of MTT and SRB, and the principle is as follows:
MTT assay: based on the metabolic reduction of 3- (4, 5-dimethylthiozol-2-yl) -2, 5-diphenylterazolium bromide, NADP-related dehydrogenase is present in the mitochondria of living cells, yellow MTT can be reduced to Formazan which is insoluble and bluish-purple, dead cells do not have the enzyme, MTT is not reduced, after dissolving the Formazan with DMSO, optical density of characteristic wavelength can be measured by a microplate reader, and relevant data processing can be carried out to conclude.
SRB assay: sulforhodamine B is a pink protein-binding dye, soluble in water, binds to basic amino acids in biological macromolecules, gives a good linear relationship between OD reading at 515nm and cell number, and quantifies drug loading and data on cell number.
Analyzing human liver cancer Bel-7402 cell strain, human stomach cancer BGC-823 cell strain, and human nasopharyngeal cancer KB cell strain by SRB analysis, analyzing human leukemia HL-60 cell strain by MTT analysis, and determining IC50Values, results are shown in table 1, and the conclusion is that: according to the data in the table, the anticancer drug of the invention has higher anticancer activity to human liver cancer and in vitro activity IC to human gastric cancer and leukemia50IC's with values greater than cisplatin50Can be used as candidate compound of anticancer drug.
TABLE 1 test data of in vitro activity of organotin complex anticancer drugs
| Human liver cancer | Human stomach cancer | Human nasopharyngeal carcinoma | Human leukemia | |
| Sample numbering | 08-31 | 08-31 | 08-31 | 08-31 |
| Sample IC50(μM) | 5.0 | 6.6 | 10.821 | 5.8 |
| Cis-platinum IC50(μM) | 7.7 | 6.8 | 3.2 | 6.0 |
| Method of producing a composite material | SRB | SRB | SRB | MTT |
| Cell line | Bel-7402 | BGC-823 | KB | HL-60 |
Claims (1)
1. An application of an organotin coordination compound with the following structural formula in preparing a medicament for treating gastric cancer, nasopharyngeal carcinoma, human liver cancer or leukemia:
wherein,nbu represents n-butyl.
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| CN101838284B (en) * | 2010-05-25 | 2011-12-07 | 聊城大学 | Dibutyltin oxide coordination compound and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1356309A (en) * | 2001-11-29 | 2002-07-03 | 山西医科大学 | Match of dihydroxytin monoclear p-chloro, p-fluoro or p-methoxyl-benzoyl hydroxamate and its synthesizing process |
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| CN1356309A (en) * | 2001-11-29 | 2002-07-03 | 山西医科大学 | Match of dihydroxytin monoclear p-chloro, p-fluoro or p-methoxyl-benzoyl hydroxamate and its synthesizing process |
Non-Patent Citations (4)
| Title |
|---|
| Hongyun wang et al..Di- μ3-oxido-bis(μ2-quinaldato-κ2O:O)bis(quinaldato-κ2N,O)tetrakis[di-n-butyltin(IV)].《Acta Crystallographica Section E》.2007,第E64卷m197-m198以及supplementary materials. * |
| Hongyunwangetal..Di-μ3-oxido-bis(μ2-quinaldato-κ2O:O)bis(quinaldato-κ2N O)tetrakis[di-n-butyltin(IV)].《Acta Crystallographica Section E》.2007 |
| 尹汉东等.有机锡化合物二{氧合-二[杂环羧酸二丁基锡(IV)]}的合成、表征和二{氧合-二[2-噻吩甲酸二丁基锡(IV)]}的晶体结构.《有机化学》.2004,第24卷(第7期),770-774. * |
| 胡浩斌.有机锡配合物的抗癌活性研究进展.《陇东学院学报(自然科学版)》.2004,第14卷(第2期),48-53. * |
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